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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Extracellular vesicles (EVs) play pivotal roles in tumor progression and metastasis by mediating intercellular communication within the tumor microenvironment. In this study, we identified two novel EX cargo proteins—UBE2NL and HIST2H3PS2—derived from highly aggressive epithelial ovarian cancer (EOC) cells and mesenchymal-type ovarian stromal progenitor cells (MSC-OCSPCs) but absent in less aggressive SKOV3 cells. Quantitative proteomic profiling via LC-MS/MS and TCGA-integrated analysis revealed that high expression of these genes correlated with advanced tumor stages and poor overall survival in EOC, and high HIST2H3PS2 expression predicted poor survival in endometrial cancer (EC). Functionally, UBE2NL and HIST2H3PS2 overexpression promoted EOC cell invasiveness, which was further enhanced by EX-mediated autocrine and paracrine effects. In contrast, the knockdown of UBE2NL reduced cell invasiveness and prolonged mouse survival in vivo. Moreover, HIST2H3PS2-enriched EXs significantly increased peritoneal dissemination and ascites in murine models. These findings suggest that EX-packaged UBE2NL and HIST2H3PS2 drive tumor aggressiveness and metastasis in gynecologic cancers, highlighting their potential as prognostic biomarkers and therapeutic targets.

Details

Title
Extracellular-Vesicle-Associated UBE2NL and HIST2H3PS2 Promote Tumor Aggressiveness and Metastasis in Gynecologic Cancer
Author
Ho, Chih-Ming 1   VIAFID ORCID Logo  ; Ting-Lin, Yen 2   VIAFID ORCID Logo  ; Chang Tzu-Hao 3   VIAFID ORCID Logo  ; Shih-Hung, Huang 4 

 Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan, School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City 242, Taiwan 
 Department of Medical Research, Cathay General Hospital, Sijhih, New Taipei City 221, Taiwan; [email protected], School of Medicine, Taipei Medical University, Taipei 110, Taiwan 
 Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei 110, Taiwan; [email protected] 
 Department of Pathology, Cathay General Hospital, Taipei 106, Taiwan; [email protected] 
First page
4833
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3211996660
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.